Albumin nanoparticles deliver mRNA on target

Abstract

Traditional mRNA vaccines use lipid nanoparticles (LNPs) conjugated to polyethylene glycol (PEG) for delivery of mRNA to cells. However, PEG-LNPs can accumulate in the liver and in rare cases might result in hepatotoxicity, particularly with repeated injections in high doses. Now, writing in Nature Materials, Guocan Yu, Xiaoyuan Chen, Gong Cheng and collaborators describe an albumin-recruiting LNP system that prevents uptake by hepatic tissue and is effective in preclinical models of cancer and infectious diseases.

To investigate their biodistribution mechanisms, the authors also compared the behaviour of both types of LNP following intramuscular injection. Consistent with their high lymphatic drainage efficiency, EB-LNPs mostly travelled from the injection site into the intramuscular lymphatic vessels, whereas PEG-LNPs directly entered the bloodstream via intramuscular blood vessels and circulated to the liver. Once in the lymphatic system, EB-LNPs were internalized by dendritic cells, a type of immune cell that engulfs antigens and presents them on their surface for activation of the adaptive immune system. These findings indicate that EB-LNPs hold great promise as an efficient and safe delivery mechanism for mRNA vaccines.